Extended Data Fig. 10: Proposed Model.

(a) The muscle atrophy of the Quadriceps around OA joints is commonly accompanied by cartilage degeneration in clinical settings during the progression of OA. The pathological characteristics of Quadriceps muscle atrophy can be summarized as a reduction in CSA, an increase in immune cells, particularly macrophages, and enhanced tissue vascularization. (b) In the chronic inflammatory microenvironment of quadriceps muscle atrophy, macrophages gradually infiltrate skeletal muscle cells (SkMCs) tissues, where they may phagocytose both red blood cells and SkMCs to degrade hemoglobin into heme within the cells. The senescent macrophage exhibits an accumulation of iron ions in the tissue environment and facilitates ferroptosis of SkMCs through iron overload. (c) Mechanistically, iron overload induces mitochondrial damage in SkMCs, leading to a decrease in Asparagine metabolites and subsequent inhibition of the mTORC1-HMGCR signaling pathway, thereby impairing CoQ10 synthesis and ultimately compromising ferroptosis defense systems. (d) CoQ10 has been extensively utilized in the treatment of cardiac diseases due to its myocardial nourishing properties and ability to enhance myocardial function. Based on our findings, systemic supplementation of CoQ10 effectively inhibits ferroptosis in SkMCs within the Quadriceps of OA joints, thereby reducing muscle atrophy and mitigating articular cartilage lesions during OA progression. This perspective offers a potential strategy for addressing OA-related muscle atrophy.